Characterization of the Streptococcus mutans Operon Reveals Its Role in Riboflavin Import and Response to Acid Stress.

utilizes numerous metabolite transporters to obtain essential nutrients in the "feast or famine" environment of the human mouth. and most other streptococci are considered auxotrophic for several essential vitamins including riboflavin (vitamin B), which is used to generate key cofactors and to perform numerous cellular redox reactions. Despite the well-known contributions of this vitamin to central metabolism, little is known about how obtains and metabolizes B The uncharacterized protein SMU.1703c displays high sequence homology to the riboflavin transporter RibU. Deletion of hindered growth in complex and defined medium in the absence of saturating levels of exogenous riboflavin, whereas deletion of cotranscribed alone had no apparent effect on growth. Expression of in a riboflavin auxotroph functionally complemented growth in nonsaturating riboflavin conditions. was also able to grow on flavin adenine dinucleotide (FAD) or flavin mononucleotide (FMN) in an SMU.1703c-dependent manner. Deletion of and/or impacted acid stress tolerance, as all mutants showed improved growth at pH 5.5 compared to that of the wild type when medium was supplemented with saturating riboflavin. Cooccurrence of and , a hypothetical PAP2 family acid phosphatase gene, appears unique to the streptococci and may suggest a connection of SMU.1702c to the acquisition or metabolism of flavins within this genus. Identification of SMU.1703c as a RibU-like riboflavin transporter furthers our understanding of how acquires essential micronutrients within the oral cavity and how this pathogen successfully competes within nutrient-starved oral biofilms. Dental caries form when acid produced by oral bacteria erodes tooth enamel. This process is driven by the fermentative metabolism of cariogenic bacteria, most notably Nutrient acquisition is key in the competitive oral cavity, and many organisms have evolved various strategies to procure carbon sources or necessary biomolecules. B vitamins, such as riboflavin, which many oral streptococci must scavenge from the oral environment, are necessary for survival within the competitive oral cavity. However, the primary mechanism and proteins involved in this process remain uncharacterized. This study is important because it identifies a key step in riboflavin acquisition and cofactor generation, which may enable the development of novel anticaries treatment strategies via selective targeting of metabolite transporters.